Neoplasia is an abnormal proliferation of cells within a tissue or an organ, resulting in a structure known as a neoplasm. Tumor is a neoplasm that has formed a lump; while neoplasm may not form a lump, for example cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and leukemia. Neoplasm may be benign, however it can also be malignant. A benign neoplasm includes, for example, leiomyoma or uterine fibroids and melanocytic nevi or moles. A malignant neoplasm includes, for example, teratoma, also various kinds of cancer, including breast cancer.
Breast cancer is the second most occurring cancer in Indonesian women after cervical cancer. Men could also suffer from breast cancer even though the chance is less than that of women. Breast cancer treatment that is commonly used is a surgical removal of the cancer tissue, followed by, if necessary, a chemotherapy or radiation treatment.
Inflammation is a form of a nonspecific response of immune system to a damaged cell. Inflammation is usually characterized by redness, pain, warmth and swelling. There are a number of components which could cause inflammation, however, the component which is closely related to inflammation is prostaglandin, especially the prostaglandin E2 (commonly abbreviated as PGE2). The concentration of PGE2 could be suppressed by nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by inhibiting cyclooxygenase enzyme, abbreviated as COX, which is an enzyme acting in the formation of prostanoids, including prostaglandins, prostacyclins, and thromboxanes. COX has two isoforms, named COX-1 and COX-2.
COX-1 is a constitutive enzyme, its concentration is stable within a body, it can be found in a majority of tissues, it converts arachidonic acid (AA) to prostaglandin. The prostaglandin then stimulates normal body functions such as secreting mucus in intestine. Normally, COX-2 is undetectable in normal cells, however its expression is inducible. COX-2 plays an important role in inflammation, because its involvement in producing prostaglandin for the inflammatory response. In cells, AA is also important for prostaglandin synthesis. AA from a phospholipid membrane is released into a cell by the enzyme phospholipase A2 (PLA2).
Angiogenesis is a physiological process involving the formation and growth of new blood vessels from pre-existing vessels. Angiogenesis process is a normal process in growth and development, however, it is also a fundamental step in the transition of tumors from a dormant state to a malignant state. Angiogenesis is stimulated by several chemical compounds, one of which is the vascular endothelial growth factor (VEGF). VEGF has a major contribution to angiogenesis by increasing the number of capillaries. VEGF comprises of VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PlGF (Placenta Growth Factor). Recently it was discovered that VEGF-E and VEGF-F are also coded by virus. Based on some literatures, there is a positive correlation at mRNA level between COX-2 and VEGF-C in the tissues and cells of breast cancer.
The fruits and leaves of Phaleria macrocarpa plant, also known as Mahkota Dewa, have been used by Indonesian people to overcome various symptoms and diseases, to include treatment of cancer. The Indonesian Patent Application No. P00 2005 00077 taught that the flavonoid of water-processed extract of Mahkota Dewa (Phaleria macrocarpa) has the characteristics of an anticancer, based on its ability to reduce the tyrosine kinase activities, its antioxidant activities, and its activities against HeLa cancer cells proliferation.
Within the current invention, the data will be described showing the effects of Phaleria macrocarpa extract as antineoplastic agent in inhibiting cell growth and its ability to induce breast cancer cell death via the mechanism of apoptosis. In addition, the effects of Phaleria macrocarpa extract as anti-inflammatory and antiangiogenic agent will also be described.